Plasma Vitamin C and Risk of Late Graft Failure in Kidney Transplant Recipients: Results of the TransplantLines Biobank and Cohort Study

Recent studies have shown that depletion of vitamin C is frequent in outpatient kidney transplant recipients (KTR) and that vitamin C is inversely associated with risk of death. Whether plasma vitamin C is associated with death-censored kidney graft failure remains unknown. We investigated KTR who participated in the TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study. The primary outcome was graft failure (restart of dialysis or re-transplantation). Overall and stratified (p(interaction) < 0.1) multivariable-adjusted Cox regression analyses are presented here. Among 598 KTR (age 51 +/- 12 years-old; 55% males), baseline median (IQR) plasma vitamin C was 44.0 (31.0-55.3) mu mol/L. Through a median follow-up of 9.5 (IQR, 6.3-10.2) years, 75 KTR developed graft failure (34, 26, and 15 events over increasing tertiles of vitamin C, log-rank p < 0.001). Plasma vitamin C was inversely associated with risk of graft failure (HR per 1-SD increment, 0.69; 95% CI 0.54-0.89; p = 0.004), particularly among KTR with triglycerides >= 1.9 mmol/L (HR 0.46; 95% CI 0.30-0.70; p < 0.001; p(interaction) = 0.01) and among KTR with HDL cholesterol >= 0.91 mmol/L (HR 0.56; 95% CI 0.38-0.84; p = 0.01; p(interaction) = 0.04). These findings remained materially unchanged in multivariable-adjusted analyses (donor, recipient, and transplant characteristics, including estimated glomerular filtration rate and proteinuria), were consistent in categorical analyses according to tertiles of plasma vitamin C, and robust after exclusion of outliers. Plasma vitamin C in outpatient KTR is inversely associated with risk of late graft failure. Whether plasma vitamin C-targeted therapeutic strategies represent novel opportunities to ease important burden of graft failure necessitates further studies.